Laboratory research has shown that various ultrasound frequencies can enhance clot lysis in the presence of tissue plasminogen activator (TPA). Dr Alexandrov has obtained pilot non-randomized data indicating recanalization and recovery rates higher than can be expected from the NINDS TPA Stroke Study when TPA infusion was monitored by 2 MHz transcranial Doppler JCD) in patients with acute ischemic stroke. The goal of this proposal is to develop a practical operator- independent ultrasound device and to demonstrate its effectiveness and safety in enhancing thrombolytic therapy for ischemic stroke. Enhancing performance of TPA with inexpensive external ultrasound can result in earlier recanalization, accelerated patient recovery and improved outcome. Major objectives of this proposal are: 1. to develop an operator- independent ultrasound device for diagnosis and monitoring of intracranial occlusions 2. to compare rates of recanalization and recovery between patients treated with standard TPA dose versus patients treated with TPA and also continuously monitored by the operator-independent ultrasound device in phase II-III randomized trials. Dr Alexandrov will learn biometry and clinical trial design methods under supervision of Dr James Grotta, UT-Houston, TX and develop the device under the supervision of Dr Merrill Spencer, Institute for Applied Physiology in Medicine, Seattle, WA. Also under Dr Grotta's supervision, Dr Alexandrov will then design and execute a randomized phase II trial. The primary specific aims for this pilot phase II study are: 1. To determine complete recanalization and early clinical recovery rates in patients treated with intravenous TPA and continuously monitored with an external ultrasound compared to those treated with standard TPA dose alone. 2. To determine if continuous monitoring of TPA infusion with external ultrasound is safe and will not result in higher rates of symptomatic intracerebral hemorrhage compared to controls. Data generated during this phase II trial will form the basis for a design of a properly powered multicenter phase III trial. Time table includes: Courses in biometry, statistical methods and research design (1st year, 2nd year) Device development, adjustments and pilot patient studies (1st year, 2nd year) Phase II randomized trial and preliminary data analysis (2nd year, 3rd year) Manuscript preparation, data presentation and follow-up grant writing (4th year)